Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang...

35
Molecular Phenotype Guided Therapy for Pancreatic Cancer David Chang Clinical Senior Lecturer Wolfson Wohl Cancer Research Centre ECMC Annual Network Meeting 14 th May 2014

Transcript of Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang...

Page 1: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Molecular Phenotype Guided Therapy for Pancreatic Cancer

David Chang Clinical Senior Lecturer Wolfson Wohl Cancer Research Centre ECMC Annual Network Meeting 14th May 2014

Page 2: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Outline

•  Cancer is heterogeneous �  APGI sequencing project (mutational landscape) �  Therapeutic implications �  DNA-damaging agents responsive phenotype

•  Lesson learnt so far and challenges ahead

Page 3: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •
Page 4: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Cancer is complex & Heterogeneous

Page 5: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

International Cancer Genome Consortium (ICGC)

CANADA• Pancreatic cancer (Ductal adenocarcinoma)• Pediatric brain tumors (Medulloblastoma)• Prostate cancer (Adenocarcinoma)

GERMANY• Lung cancer (Multiple rare subtypes) • Malignant lymphoma (Germinal center B-cell derived lymphomas)• Pediatric brain tumors (Medulloblastoma and Pediatric pilocytic astrocytoma)• Prostate cancer (Early onset)

UNITEDKINGDOM

• Bone cancer (Osteosarcoma/ chondrosarcoma/ rare subtypes)• Breast cancer (Triple negative/lobular/ other)• Chronic Myeloid Disorders (Myelodysplastic syndromes, myeloproliferative neoplasms and other chronic myeloid malignancies) • Esophageal cancer (Esophageal adenocarcinoma) • Prostate cancer

EU / UNITEDKINGDOM

• Breast cancer (ER positive, HER2 negative)

• Bladder cancer• Blood cancer (Acute lymphoblastic leukemia/ Acute myeloid leukemia) • Brain cancer (Glioblastoma multiforme/ Lower grade glioma)• Breast cancer (Ductal & lobular)• Cervical cancer (Squamous) • Colorectal cancer (Adenocarcinoma)• Endometrial cancer (Uterine corpus endometrial carcinoma)• Gastric cancer (Adenocarcinoma)• Head and neck cancer (Squamous cell carcinoma/ Thyroid carcinoma)• Liver cancer (Hepatocellular carcinoma)• Lung cancer (Adenocarcinoma/ Squamous cell carcinoma)• Ovarian cancer (Serous cystadenocarcinoma)• Pancreatic cancer (Adenocarcinoma)• Prostate cancer (Adenocarcinoma)• Renal cancer (Renal clear cell carcinoma/ Renal papillary carcinoma)• Skin cancer (Cutaneous melanoma)

UNITED STATES ITALY• Rare pancreatic tumors (Enteropancreatic endocrine tumors and rare pancreatic exocrine tumors)

CHINA• Bladder cancer (Urothelial carcinoma)• Blood cancer (Acute myeloid leukaemia and Chronic myelogenous leukaemia)• Brain cancer (Glioblastoma multiforme)• Breast cancer (Triple negative)• Colorectal cancer (Adenocarcinoma, non-Western)• Esophageal cancer (Squamous carcinoma)• Gastric cancer (Intestinal- and diffuse-type)

• Liver cancer (Hepatocellular carcinoma, HBV-associated)• Lung cancer (Squamous cell carcinoma)• Nasopharyngeal cancer (Nasopharyngeal carcinoma, Asia)• Ovarian cancer• Pancreatic cancer (Ductal adenocarcinoma) • Prostate cancer• Renal cancer (Clear cell renal cell carcinoma)• Thyroid cancer (Papillary carcinoma)

• Thyroid cancer (Papillary carcinoma)

SAUDI ARABIA

• Blood cancer (Acute myeloid leukaemia)• Breast cancer (Asian phenotype)• Lung cancer (Adenocarcinoma/ Squamous cell carcinoma)

SOUTH KOREA

Grey = Collaboration

EU / FRANCE• Renal cancer (Renal cell carcinoma) (Focus on but not limited to clear cell subtype)

MEXICO• Blood cancer (Diffuse large B-cell lymphoma)• Breast cancer (Ductal carcinoma)• Cervical cancer • Head and neck cancer (Squamous cell carcinoma of oral cavity/oropharynx/ sinonasal cavity/ hypopharynx/larynx)• Pediatric solid tumors

SPAIN• Chronic lymphocytic leukemia (CLL with mutated and unmutated IgVH) FRANCE

• Breast cancer (Subtype defined by an amplification of the HER2 gene)• Ewing sarcoma • Liver cancer (Hepatocellular carcinoma) (Secondary to alcohol and adiposity)• Prostate cancer (Adenocarcinoma)

AUSTRALIA• Ovarian cancer (Serous cystadenocarcinoma)• Pancreatic cancer (Ductal adenocarcinoma/ Neuroendocrine tumors)• Prostate cancer

JAPAN• Liver cancer (Hepatocellular carcinoma) (Virus-associated)

SINGAPORE• Biliary tract cancer (Gall bladder cancer/ Cholangiocarcinoma)

BRAZIL• Skin cancer (Melanoma)

INDIA• Oral cancer (Gingivobuccal)

Page 6: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Australian Pancreatic Cancer Genome Initiative (APGI)

Prospective observational cohort study design (350 PDAC)

���������������

����������

Biankin Grimmond

Page 7: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

�������

����������� �

����������� ��

������

���������� �����������

������

������� �����

������������!"��#$%��&"����#$%��&�

����'��������(���� ����� ���)����� ���������

���*�������

+� ,! �+��������,��� "��� ,! �

��&�

��������(���� ����� �-����.�

��!�

�����

���������

������ � ����������� ����

/$0�1$2�1,������ !���"�*3$%���&�����*�

��������� �������

��������&�����*��

������ �������

Page 8: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

4�

�4�

�4�

�4�

�4�

�44�

��4�

�5

6�

�� �

675�

��

7��

� �

��8�

��

9��

�� 7

:���

� �

67��

� 6�

���

5�

��5�

�5�

���

��7

�� �

�58�

� �

����

87

����

5��

�� 5

��5�

�� �

����

�7��

� ;

���

� 6�

��5�

���

���

�� �

;���

6��<

�� �

�8�4

� �

����

5�

� �

�5�57

6�4

� �

<;�

� 6�

���

9�

���

�<

����

5�

���

��;�

�� �

� �

6�9

5���

675

�5��

67

�� �

6�5�

�4�

�8�

�� �

����

���

��

�� �

�7

�� 7

���

�� �

7

�� �

��8�

�� �

�6��

� 5

��4

5� 9

��

86��

5� <

����

���

�� �

6���

����

5�7

6��

��6

���

� 6<

75�

��

Genomic Landscape of PDAC

•  KRAS (93%), •  TP53 (42%), •  SMAD4 (20%) •  MLL3 (8%) •  PCDH15 (7%) •  TGFBR2 (6%) •  SF3B1 (5%) •  ARID1A (5%) •  ATM (5%) •  CDKN2A (4%)

•  Whole Exome Capture and Sequencing + CNV (n=142) (Biankin et al., Nature 2012)

•  38 of 79 (> 1 mutations) identified by Jones et al. (2008 n=24) •  186 of 998 of Jones et al. (2008) •  19% overlap •  1456 novel genes mutated

Ave Coverage: 68 - 200x 90% > 15 independent reads CNV: 10% of Genome

� !��"��#$�%%& �"!�$& �������� ���� ������ �� � ��������� ��

������ ��� �������� ����

������� ���

Page 9: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

��

���

����

.#%/

��0��

�13

.$�%

�/+

%3��

%# 3�%

��$

����

�#$

����

3$%�

��

.3+%

��$

%/�

/�%�

���0

���

3/��

0##1

�%�

31�/

�+

%0�.

��0#

� ��

0�1�

�01

$��

��1�

30����0

�0�

0#��

0�0#

#��%

��

10 +

���$

�.�

�0�%

����

#1��

+3�

%��

+���1

�1%

1$%

��/%

1/�

/�1�

1�

�/��

%�%1

2#�

�/%

+3�

��+

3$�

�$���

�.1

�3�

�%�

1%��

%�11

���#

1%�

3�1.

��+�1

�0��

���

��

/�����

/���

+��/���

Known oncogenes: KRAS: 93% GNAS: 7% SF3B1: 4% Known TSG: TP53 70% CDKN2A 24% SMAD4 22% ARID1A 16% BRCA1 4% SLIT2 4%

���

Non-Silent Point Mutations in PDAC (WGS)

Waddell, Pajic, Patch, Chang et al, in submission

10%

Page 10: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Multiple Subtypes : Implications for Development of Therapeutic Strategy Heterogeneity = Therapeutic development implications

Page 11: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

����������� ����������������������������������������������������

� � ��� ��������������������������������� !"#�$�

�,��/������# �����1 ����� ���� �-�

Page 12: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Fool’s Gold or Lost Treasures??

Stewart & Kurzrock, BMC Cancer 2013

Not Approved Approved

Target in 15% Target in 16.7%

P = 0.06 P = 0.04

(Exceptional) Responders

n = 11

Simulation of 334 NSCLC patients (actual survival) in each arm (668 in total)

Page 13: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

/�� ����� �"���� ��1,��������/������

Page 14: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

� ��������������� ����� �

��� ����3*�%�

��� ����3*���

��� ����3*�1�

��� ����3*�3�

$�?���*� ��

����3*���

��� ����,������� ���,����� ,���*, � �� ��� �

Page 15: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

����� �!����#�������@��

3$%�3���*��

%�'A���#�#�������@��

��!A0�� � ��� �#�������@��

�A�����1����� �!����#�������@��

��#��%�� �����

+���%�� �����

%�+�� � ���

0��+�� �

���*�,�*���,�!� ��#�������@��

���#�%�� �����

0�.B1%�� � ���%�� �����

1/�)#�� � ���

#�1.�%�� �����

13.C�%�� �����

/�.))��.�)�� �

$�������'����

%�'���! ��0,��� !�������0�����'��1�����

� ������,�� -��-��������.��� �������� ��-� ��

$���

����� �!����#�������@��

3$%�����*��

%�'A���#�#�������@��

���A0�� � ��� �#�������@��

�A���1���#�������@��

%&'"�%�� �����

�&��%�� �����

()('�%�� �����

*�+,������-%���

'.�+�%�� �����

����� � ���

*�&/�� ����*�,�*�%�'@� ���

�0( '�� � ���

�$+1�%�� �����0�+ -2+3 �����%�� �����

*�''�'�0�

Page 16: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Approach •  $�D�)�����/�•  0,��� !��A �A*��� !������ !����

•  3$%A����*��*��*�� ��������@���,��� !�������� ��'� !��!� ��'� !� �*�� ,�����@��� !�!� ��@��E�

///�////�/�/�////���/��/��///��//�����/�/�/�������������/�����/�/�������������/�������������/�������/��������/���

Waddell, Pajic, Patch, Chang et al, in submission

•  0 �'�������������������,���!!�,�*,�3'�����*�� ����"��*�?� ,��@� �����*��� �! ��*������������ �'�������3'���3$%����� ��������� ,?�!�*�����

��0����

Page 17: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Chang et al, Nat Rev Cancer, 2014

���.������1� -������ �-��. ���

Pajic & Chang et al, in preparation

Page 18: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

��*�'�*�%�'���! ��+� �� ��0,��� !����

HER2 Amplified (2%): GEM + Trastuzumab KRAS wild type (5%): GEM + Erlotinib BRCA2 Germ Line mutant (3%): MMC + Capecitabine

Initially direct recruitment of ICGC patients Then panel-based screening

Page 19: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

•  Logistically demanding: tissue acquisition, QC, drugs •  Patients randomised to standard of care withdraw and buy

drug themselves •  Screening time (main problem is sample delivery) •  Sample variability (different path labs) •  Low prevalence phenotypes (need to screen large numbers) •  Screening cost (genome maybe cheaper, bioinformatics still

the same)

������������ �FGHI��JK�

Page 20: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

•  Patients without an actionable phenotype (what is best SOC?) •  Social and ethical implications with sequencing (framework for

return of results) •  Change of technology (re-validation) •  Lots more to be learnt & lots more challenges ahead

������������ �FGHI��JK�

Page 21: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Biobanking & QC

��L��������������4�������������

1. Independent Pathological review in Australia, Italy and USA.

2. 5mm3 frozen blocks of Tumour are sectioned to locate non-tumour tissue.

3. Tumour rich regions are dissected form block and DNA/RNA extracted

Page 22: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

������������G���2�� ������ � �����34���� �������������������3��2� �2������ ������ ������������������� ���03�� �����$ �$M ��������0� ������$0�� ������0�M�0� ������$�N����

����� ���������������3��2� �2��������������MM�*������ Expressed Fusion transcript ATE1 – KLRAQ1 �

������������������������5�� ���������*������

���������2���� ������*����1��������

��2��� �2����2������ �%�11� �����%3%+�����%+%1�����M�%�N� �������3�� 11M �����1M������1������N��1%1$%�1 �����1%0$�� �����1�$0� �����1��1�� �����1�1� ������ +3� ������0 �M ���!1" �����.� M3�� �����..�� ������+3� ��������0�.M13 �����0�3$ ����� 0%���������10M ������1��%� �������+���� ������$�NM� ������$��M��

How to integrate detailed molecular information into clinical practice: Molecular MDT

Page 23: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

0.2

510

−0.9

810

−1.310

−2.1

10

−3.6

10

−6.7

10

−12

0.0

45

0.1

0.2

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

1p36.1

31p36.1

31p35.3

1p34.1

1p32.3

1p31.1

1p31.1

1p21.3

1p13.2

1q21.1

1q31.3

1q32.1

1q32.2

2q31.1

2q32.3

3p26.3

3p25.1

3p24.1

3p23

3p14.3

3p14.2

3p14.1

3p14.1

3p13

3p13

3p12.3

3q11.2

3q13.3

13q24

4p16.3

4p15.3

14p11

4q13.1

4q13.1

4q31.2

14q32.2

4q34.1

5q14.2

5q14.3

5q31.1

6p25.3

6p25.1

6p23

6p21.3

36p21.3

26q12

6q15

6q16.2

6q22.3

16q25.1

6q27

7p21.3

7q21.1

17q21.1

17q21.1

17q21.1

27q31.3

17q31.3

37q36.1

8p23.3

8p23.3

8p21.2

8p12

8p11.2

18q12.1

8q12.3

8q21.1

38q23.3

8q24.1

38q24.3

9p23

9p23

9p22.3

9p21.3

9p21.3

9p21.3

9p21.3

9p21.1

9p13.2

9q21.3

39q31.1

9q34.3

10q23.3

110q23.3

310q25.3

11p15.4

11p15.4

11p15.1

11p14.3

11q13.1

12p12.3

12q12

12q14.2

12q21.2

12q21.3

112q21.3

112q24.3

112q24.3

313q13.3

13q31.3

13q33.1

14q21.1

14q21.1

14q21.1

14q31.2

15q14

16q11.2

16q23.1

17p13.3

17p13.3

17p13.2

17p13.2

17p13.2

17p13.1

17p13.1

17p13.1

17p13.1

17p13.1

17p12

17p12

17p12

17p11.2

17q21.3

217q22

18p11.3

118q21.1

18q21.2

18q21.2

18q21.2

18q22.1

18q23

19q12

20p13

21q22.1

221q22.3

22q11.1

22q12.3

0.2

510

−0.8

910

−1.110

−1.7

10

−2.9

10

−5.3

10

−10

0.0

28

0.1

0.2

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

1p31.1

1p31.1

1p21.3

1p21.3

1p21.1

1q25.1

1q25.2

1q25.2

1q25.3

1q31.1

1q31.1

1q31.1

1q31.2

1q31.3

1q41

1q41

1q41

1q42.2

2p16.3

2p16.3

2p16.3

2p12

2q22.1

2q22.1

2q22.2

2q24.1

2q32.1

2q32.1

2q32.2

3p12.3

3p12.2

3p11.1

3q13.1

13q24

3q24

3q24

3q24

3q25.3

23q26.1

3q26.1

3q26.3

13q26.3

13q28

4p15.3

14p15.1

4p15.1

4p15.1

4p12

4q13.1

4q13.1

4q13.1

4q13.1

4q13.1

4q13.3

4q22.1

4q26

4q28.1

4q28.3

4q32.1

4q32.2

4q32.3

5p14.3

5p14.3

5p14.2

5p14.1

5p14.1

5p14.1

5p14.1

5p13.3

5p13.1

5p12

5q11.2

5q14.2

5q14.3

5q14.3

5q21.1

5q21.3

5q23.1

5q34

6q12

6q12

6q12

6q14.1

6q16.1

6q16.1

6q16.1

6q16.3

7p21.3

7p21.3

7p21.2

7p21.1

7p12.3

7p11.2

7q21.1

17q21.1

17q21.1

17q21.1

17q21.1

17q21.1

17q21.1

27q21.2

7q21.3

7q21.3

7q31.1

7q31.1

7q31.3

18p22

8p22

8q21.1

18q21.1

38q23.3

8q23.3

8q24.1

28q24.1

38q24.2

29p21.1

9p13.3

10q21.1

10q21.1

10q21.3

10q25.3

11p15.2

11p14.3

11p14.1

11p12

11q22.1

11q22.1

11q23.2

12p12.3

12p12.2

12p12.1

12p12.1

12p12.1

12p12.1

12p12.1

12p11.2

212q12

12q12

12q14.1

12q14.1

12q14.3

12q15

12q15

12q21.1

12q21.2

12q21.3

112q21.3

212q21.3

313q13.3

13q21.1

13q21.3

113q21.3

213q21.3

313q21.3

313q21.3

313q21.3

313q31.1

13q31.3

13q31.3

13q31.3

14q12

14q12

14q21.1

14q21.3

14q31.2

14q31.3

15q21.2

17q12

17q24.1

18q11.2

18q11.2

18q12.1

18q12.3

18q21.2

19q12

19q13.2

21q21.2

Copy number changes

ABCC9,ADAMTS20, AMAC1L2,, BLID, BRCC3, CACNA1C, CAPN11, CENPE, COLEC11, CTCF, FRMD6, GPR137B, LEMD2, PIK3CD, PXDN, RPA1..

Mutation burden

Mutational Signature

Breakpoint Signature

Telomere status

Mutations

Genome organization

Ploidy

Clonality

Germline/Inheritance

Comprehensive Cancer Genome analysis:

(<3 days)

Evolution

��������C�����

���E

)��

�EB�

�E��

��E

C��E

L��

�E��

)E��

�)E

��)E

B��

)E��

� ��� ��

Page 24: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

/ �!��*��,������� ,�� � �� ����,�� �*!�

Page 25: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Cost of Sequencing is dropping dramatically (technology is here!!)

Page 26: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Green & Guyer, Nature 2011

Harness the Technology: From Base Pairs to Bedside

Page 27: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Knowledge Bank Approach

���������� �

�������� ��

� � ��������������

���������

�� �����-���������

���� .� ��--���� ��� ���6�

������ ��

� ������ ���

�� ��� ���6������� ��

� �� �� �����

� �������

� ������.����

Page 28: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Data Sharing at a Global Scale

http://genomicsandhealth.org/

185 organisations, 26 countries 1st meeting March 2014

Page 29: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Jeff Evans Juan Valle Andrew Biankin Sean Grimmond and more��

Smarter and more Nimble Trial Designs

Page 30: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Better Integration between Key Elements

Page 31: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Translate Research Medicine to Routine Patient Care�

•  �����*�!������•  #�* � �!�!������•  1��������@��� ���•  + '� ���,��������������•  �� �A ��� �,� ��*���� !�

•  % ��,� ��*��"�! �� ��������&������ �� !�

Page 32: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

%�"��? ��*���� ��

QCMG: Sean Grimmond Garvan: Andrew Biankin

Emily Colvin Amanda Mawson Johana Susanto Marina Pajic Mona Martyn-Smith Lorraine Chantrill Adnan Nagrial Venessa Chin

Bioinformatics: John Pearson Lynn Fink Darrin Taylor David Wood Conrad Leonard Oliver Holmes Christina Xu Matthew Anderson Scott Wood Sarah Song Felicity Newell

GenomeSeq: David Miller Tim Bruxner Craig Nourse Ehsan Nourbakhsh Suzanne Manning Angelika Christ Ivon Harliwong Senel Idrisoglu

Genome Biology: Nic Waddell Karin Kassahn Ann-Marie Patch Katia Nones Nicole Cloonan Anita Steptoe Shivangi Wani Keerthana Krishnan Jason Steen Muhammad Fadlullah Kelly Quek

Rob Sutherland Liz Musgrove Roger Daly James Kench

Chris Scarlett Marc Jones David Chang Jianmin Wu Anthony Gill Page Tobelman Jeremy Humphris Mark Pinese Mark Cowley Angela Chou Lorraine Chantrill Adnan Nagrial Venessa Chin

Amber Johns Scott Mead Michelle Thomas Chris Toon Mary-Anne Brancato Cathy Axford

QCMG: Sean Grimmond Garvan: Andrew Biankin

APGI collaborators & patients

Page 33: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

Acknowledgements

Verona: Aldo Scarpa Claudio Bassi Paolo Pederzoli Rita Lawlor

Johns Hopkins: Ralph Hruban Jim Eshleman Anirban Maitra Chris Iacobuzio-Donahue

Sanger: Ludmil Alexandrov Serena Nik-Zainal Peter Campbell Mike Stratton

Glasgow: Ross Carter Colin Mackay Nigel Jamieson Euan Dickson Mark Duxbury Karin Oien Jane Hair Fraser Duthie Jeff Evans

Page 34: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •
Page 35: Molecular Phenotype Guided Therapy for Pancreatic Cancer€¦ · Pancreatic Cancer David Chang Clinical Senior Lecturer ... • Breast cancer (Triple negative/lobular/ other) •

�,��"�!�����!���#��'���